Grant: Project Grant

Infertility is an important human health problem that affects about 16% of couples worldwide; half of these cases can be traced to men. The diagnosis and treatment of this health problem is difficult because in 37-58% of cases the causes are not known. Infertile men often have high levels of reactive oxygen species (ROS) in their semen. These molecules are normally produced by the cell; but when they are present in high amounts, they become toxic. As men age, spermatogenesis is affected resulting in the production of fewer spermatozoa; these spermatozoa show impaired function. Because of professional and/or work priorities, men are planning to have children around or after their 40s. This deliberated delay may impact negatively on their success to achieve fatherhood or could be the cause of transmitting defects to their children. Spermatozoa, as other cell types, can cope with certain levels of ROS by removing those with antioxidants. However, if the antioxidant amount is low and or the production of ROS is too high, then toxic effects can be observed in the sperm. This proposal is focused on the 1-Cys peroxiredoxin (PRDX6), the unique member of the PRDX family of antioxidant enzymes with peroxidase and calcium-independent phospholipase A2 activities and its role in the protection of the male reproductive tract against the toxic effect of high levels of ROS. Spermatozoa from infertile men have low levels of PRDX6 and mice lacking PRDX6 are subfertile and unable to fertilize oocyte and produce embryos in vitro. Furthermore, these abnormal reproductive outcomes worsen as the mice age. Understanding the role of PRDX6 in spermatozoa under physiological conditions will allow us to seek for therapeutic strategies to keep the levels of ROS at desirable physiological levels in infertile young and aging men seeking fatherhood.